Clinical Case Summary

Introduction: The risk of fungal infection in IBD seems to be low, and mainly related to immunosuppression, but morbidity and mortality are high. We report a case of pulmonary aspergillosis in a patient with ulcerative colitis under biologic treatment.
Case: A 65-year-old woman was admitted with acute severe ulcerative colitis as a first presentation. Intravenous methylprednisolone did not manage a significant clinical improvement, ultimately requiring intravenous infliximab therapy. She was discharged with oralprednisone taper regimen. Two months later, she was admitted with SARS-COV-2 pneumonia with bacterial superinfection. After discharge, infliximab infusion was restarted. Four months later, she developed dry cough and underwent a chest CT scan showing a partially cavitated round lesion in the lung. Infliximab was suspended until further investigation. A bronchoalveolar lavage showed inflammation without malignant cells. Transthoracic lung biopsy revealed fungal structures consistent with Aspergillus. An aspergilloma was diagnosed and clinical surveillance was decided, since the patient was unfit for surgery. Six months later, the patient was admitted with acute severe ulcerative colitis. After multidisciplinary discussion of therapeutic strategy with our Infectious Disease and Pneumology teams, the patient was started on intravenous methylprednisolone along with voriconazol, with a complete clinical response. Two weeks later, a chest CT scan showed reduction of the lesion size and the patient started Ustekinumab for maintenance of remission. After three weeks of treatment with voriconazol, isavuconazol was substituted for voriconazol because of severe pancytopenia and hepatotoxicity. She was discharged with oral prednisone taper regimen, isavuconazol and ustekinumab.
Discussion: This case highlights the fact that opportunistic infections in immunocompromised IBD patients require a high degree of suspicion and pose difficult therapeutic decisions.

Clinical Case Summary

A 77-year-old man underwent liver transplantation in 2008 due to alcoholic cirrhosis associated with hemochromatosis, and was taking tacrolimus and mycophenolate mofetil since that.
He was admitted in the Emergency Department in February 2023 with right upper quadrant abdominal pain and diarrhea for one week. Abdominal computed tomography(CT) showed ileal thickening. Laboratory tests revealed leukocytosis(19,000 leukocytes/mm3) and elevated C-reactive protein(16 mg/dL). Acute gastroenteritis was assumed and he was discharged on metronidazole with clinical improvement. One month later, he returned to the Emergency Department with abdominal pain for two days. CT revealed concentric wall thickening of the last ileal loop and a probable enteromesenteric fistula. He was admitted for further evaluation. Colonoscopy revealed deep mucosal ulceration of the terminal ileum. After colonoscopy, his abdominal pain worsened, so he repeated the abdominal CT, which showed a new organized collection in the right flank measuring 63 mm and small gas bubbles of pneumoperitoneum in the right upper quadrant. He underwent ileocecal resection with terminal ileostomy, and the histopathological evaluation revealed a neoplasm composed of atypical lymphoid proliferation, with positive immunohistochemistry for CD45, CD20, CD79a, BCL2, and BCL6, compatible with diffuse large B-cell lymphoma. After staging and exclusion of distant disease, the patient was proposed for chemotherapy following reduction of immunosuppression.
The clinical presentation of Inflammatory Bowel Disease can be quite heterogeneous and several pathologies can mimic its clinical, endoscopic, and/or histological findings. This case illustrates the importance of considering the diagnosis of small bowel lymphoma as a differential diagnosis of Crohn's disease, especially in elderly patients with risk factors, such as chronic immunosuppression.

Introduction

Inflammatory bowel disease (IBD), ulcerative colitis (UC) and Crohn’s disease (CD), is a group of chronic inflammatory disorders. Biologics are indicated for patients failing conventional maintenance therapy with moderate to severe activity. Different routes of administration, intravenous (IV), subcutaneous (SC) or oral have been approved. For chronic diseases such as IBD, some patients may prefer self-administered SC dosing to IV dosing as a less time-intensive and more convenient treatment option.

Aims & Methods

This study aims to evaluate evaluate the success of infliximab subcutaneous administration after switching from intravenous administration in IBD patients. The transition from IV to SC administration was proposed to 60 IBD patients in clinical remission. Data on medical history and laboratory tests were collected from electronic health records. Moreover, patients filled a paper questionnaire 8 weeks after the switch focused on the level of satisfaction and onset of adverse event (AE).

Results

Overall 60 patients were enrolled for switching from IV to SC therapy. Most of patients (>80%) did not experience any difficulties in handling the device and respected the correct time-table of administration. The switch was a complete success in 50 out of 60 patients (83.3%). Ten patients stopped subcutaneous formulation: five of these switched back to intravenous formulation for adverse event or patient’s preference, four swap or swop to other therapy and one withdraw from biologic. No predictor of loss of response was found at multivariate analysis. Faecal calprotectin and C-reactive protein values significantly improve after the switch at 3, 6 and 12 months (p= 0.03, p= 0.004, p = 0.01 and p= 0.06, p= 0.001, p= 0.007 respectively). About 16.7 % of patients had at least one side effect after switching. Local pain and swelling at site of injection were the most common AEs. The vast majority of AE were mild and lasted only a few days. No serious AEs were reported and no patient was hospitalized.

Conclusion

Effectiveness of switching from intravenous to subcutaneous infliximab administration in IBD patients is confirmed in our real world cohort of patients.

Introduction

In Australian patients receiving intravenous (IV) infliximab (IFX) treatment, 44% of patients do not respond to standard regimen and require dose escalation within a year. The REMSWITCH (6-month evaluation) and REMSWITCH-LT (18-months evaluation) investigated the effectiveness of switching from IV to subcutaneous (SC) IFX in patients with inflammatory bowel disease (IBD) who received standard and dose-escalated IV regimen. The two studies concluded that a fixed dose of 120 mg Q2W is feasible, safe and well-accepted leading to a low risk of long-term relapse in patients with escalated IV doses except for those on 10mg/kg/4weeks regimen. In this study, we developed a model to estimate the financial implications of switching.

Aims & Methods

Clinical efficacy parameters were derived from the REMSWITCH and REMSWITCH-LT studies and applied to the Australian context. Number of Australian patients who are on IFX, the proportion of patients on dose escalated regimen, and cost parameters were identified from the published literature or publicly available resources. A financial model was developed based on the assumption that a cohort of patients will receive either IV or SC IFX, and the analysis concluded with the cost difference.

Results

The model assumes that a total of 5.6K patients are receiving IV IFX, with 44.2% of them receiving dose escalation and/or shortened interval of IV IFX. The model produced 6 months and 12 months results, suggesting savings between 582 and 882 AUD per patient, respectively, and equates to a yearly societal savings of 5 million AUD.

Conclusion

IFX SC deserves premium over IFX IV, given that the novel formulation offers tangible and intangible benefits that originator Remicade and biosimilars cannot provide. There is a concern regarding the affordability of SC IFX because it is generally priced higher than IV IFX, which has many biosimilars on the market. However, this study asserts that fixed dosing of 120mg of IFX is cost-saving for society, considering highly prevalent practice of dose escalation and/or shortened intervals of IFX regimen.

Introduction

Aims & Methods

Results

Conclusion

References

Introduction

Inflammatory bowel disease (IBD) describes two chronic inflammatory intestinal diseases: Ulcerative Colitis (UC) and Crohn’s Disease (CD). Treatment of these conditions is often through immunosuppression to induce remission then maintenance. Cytomegalovirus (CMV) is a virus commonly found latent in all humans with seroprevalence rates existing between 40-100% depending on geographical location (1). Pathological reactivation of CMV is triggered by inflammation and immunosuppression; both present in the pathogenesis and treatment of IBD respectively (2). Consequentially, CMV reactivation occurs in IBD flare-ups around a rate of 25% (2) and greater than 30% in steroid-refractory patients (1, 3). Whether CMV reactivation is associated with escalating medical therapy, further hospital admissions, and worse clinical outcomes such as toxic megacolon or colectomy when compared to non-CMV associated flare-ups remains controversial. As such, the aims of this study were to follow up patients with IBD following an index episode of CMV colitis and analyse disease progression, relapse of CMV colitis, and clinical outcomes.

Aims & Methods

As such, the aims of this study were to follow up patients with IBD following an index episode of CMV colitis and analyse disease progression, relapse of CMV colitis, and clinical outcomes.
A retrospective study of patients treated at Royal Melbourne Hospital, Parkville, Australia treated between 2018-2023 was completed. Patients were included if they had a diagnosis of IBD, had positive immunohistochemistry for CMV on biopsy, and were treated with Ganciclovir or Valganciclovir for CMV colitis. Data collected included
demographic details and laboratory investigations at time of first episode of CMV colitis. Data regarding treatment for IBD and CMV colitis at time of CMV colitis was also collected. Outcome results were collected at 6-month and 12-month time points after first episode of CMV colitis. Fourteen patients were included in this study; 13 with UC and 1 with CD.

Results

Recurrence of CMV colitis occurred in 21% of cases at 6 months and 29% at 12 months. Additional courses of corticosteroids remained constant at 21% of cases at 6 and 12 months. Forty-three percent of patients had changed their biologic at 6 months and this stayed constant at 12 months. Similarly, 29% of patients had escalated their biologic dose at 6 months which was the same at 12 months. At 6 months, 43% of patients had been re-hospitalised due to IBD or CMV including 2 colectomies. At 12 months, these figures increased to 36% and 3 respectively. Disease remission was only achieved by 7% of patients at 6 months, increasing to 29% at 12 months.

Conclusion

While a descriptive study, our results when compared with previous studies (4) suggest that CMV colitis is a negative prognostic marker in patients with IBD, resulting in higher rates of hospitalisation, failed medical therapy requiring medication change or dose escalation, and colectomy. These risks may be greater at <6 months from index episode of CMV colitis. Further research regarding effective management of CMV colitis is needed to minimise poor outcomes in these patients.

References

1. Maher MM, Nassar MI. Acute cytomegalovirus infection is a risk factor in refractory and complicated inflammatory bowel disease. Digestive diseases and sciences. 2009;54:2456-62.
2. Kandiel A, Lashner B. Cytomegalovirus colitis complicating inflammatory bowel disease. Official journal of the American College of Gastroenterology| ACG. 2006;101(12):2857-65.
3. Cottone M, Pietrosi G, Martorana G, Casa A, Pecoraro G, Oliva L, et al. Prevalence of cytomegalovirus infection in severe refractory ulcerative and Crohn’s colitis. The American journal of gastroenterology. 2001;96(3):773-5.
4. Zhang M, Bai X, Zhang H, You Y, Lv H, Li Y, et al. The role of cytomegalovirus colitis on short- and long-term outcomes for patients with ulcerative colitis. Scandinavian Journal of Gastroenterology. 2022;57(3):282-9.

Introduction

Infections are one of the main side effects faced by patients treated with biological agents.

Aims & Methods

Objective: We aimed to determine the rates of bacterial infections among Inflammatory Bowel Disease (IBD) patients treated with biological agents in a real-life setting.
Methods: Retrospective study based on the Clalit healthcare nationwide database, which included all patients diagnosed with IBD between 1999 and 2022. Data on bacterial infections were collected for patients treated with a biologic agent (Anti_TNF, Vedolizumab and Ustekinumab) and were compared to all other IBD patients during the corresponding timeframe.
Data regarding demographics, bacterial infection events, and mortality were collected. Data were collected using the MdClone platform from the largest Health Maintenance Organization, “Clalit” in Israel.

Results

5523 IBD patients treated with Anti-TNF were compared to 29,598 patients not treated with Anti-TNF. Patients treated with Anti-TNF were younger, age 35.62±14.29 compared to 47.06±19.49 years. Anti-TNF patients had higher rates of respiratory tract infection (36.2% vs 31.2%), genitourinary system infection, 26.7% vs 23.7%, gastrointestinal tract infection (31.8% vs 21.6%), skin infection (22.5% vs 14.3%) and Ear, Nose, throat infection (31.5% vs 24.2%). 2220 patients treated with Vedolizumab compared to 35,100 not treated with Vedolizumab, patients treated with Vedolizumab had higher rates of bacterial infections, respiratory tract infection (13.5 vs 5.1%, p<0.001), genitourinary system infection, (9.7% vs 3.8%, p<0.001) gastrointestinal tract infection (12.6% vs 3.5%, p<0.001), skin infection (8.4% vs 3%, p<0.001) and Ear, Nose, throat infection (11% vs 4.4%, p<0.001). In addition, risk of bacterial infection was higher among 940 patients treated with Ustekinumab than those not treated with Ustekinumab.

Conclusion

Significantly increased risk found among IBD patients treated with biologic agents; clinicians should consider the increased susceptibility to bacterial infections when deciding which biological agent to prescribe to their asthma patients